Modeling and Characterization of Artificial Breast Cancer Tissues Using 3D Culture Methods

In an effort to develop a translational in-vitro modeling method for individual breast tumor patients, our lab has been focused of the application of natural 3D matrix materials to produce artificial tumor tissues (ATTs) in-vitro. These approaches have included both isolation and culture of primary human tumor samples as well as the use of the breast ductal carcinoma cell-line MCF-7 to model a monoculture of ductal carcinoma cells. These studies have so far focused on developing relevant culture methods and characterization of the resulting ATTs as well as cellular populations within these new structures. To date, significant results have been produced with both primary tumor tissues and the MCF-7 cell line. In the case of primary tumors, ATTs have been established with a combination of direct outgrowth of the initial tumor explant as well as a distinctive seeding of sub-nodules from the primary explant onto the scaffold. These nodules are then seen to expand and cover/fill the remaining scaffold. Perhaps the most significant observation relative to primary ATTs was the association of adipose cells with the established explant and the maintenance of these cells throughout an extended culture period of up to 6 months. In monocultures of MCF-7 cells on 3D scaffolds, distinctive patterns of growth with tissue-like features were seen throughout culture periods of up to 3 months. These have included the development of "acinar-like" structures and extended coverage of the scaffolds with MCF-7 cells. The control cell line MCF10A failed to develop these tissue-like structures and features. Morphological, ultrastructural and molecular characterization of these human breast cancer related ATTs and their respective cellular populations are ongoing.